抑制CD44（簇细胞分化抗原44）作为胰腺癌干细胞（CSC）标记物，可能是胰腺导管腺癌（PDAC）的潜在治疗方法。本研究评价了来源于多种药用植物的没食子酸鞣醇类化合物1,2,3,4,6-五-O-没食子酰基-β-D-葡萄糖（PGG）对人胰腺癌细胞系Mia-PaCa-2中CD44基准（CD44s）和CD44变体3（CD44v3）的影响，并探讨了其潜在机制。PGG表现出细胞毒性和抑制Mia-PaCa-2的增殖作用。它还抑制了具有CSC特征的成簇活性、对纤维连接蛋白的黏附和细胞迁移。PGG通过诱导p53的磷酸化并抑制NF-κB和Foxo3的作用抑制了CD44s和CD44v3的表达。Foxo3的抑制引起CD44v3的泛素化。实际上，PGG增加了蛋白酶体活性并促进了CD44v3的泛素化。PGG降低了CSC调节因子Nanog、Oct-4和Sox-2的表达，这些因子是CD44v3信号传导的下游因子。这些数据表明，PGG可能通过抑制CSC标记物在胰腺癌中具有治疗作用。©2022作者。由Informa UK Limited，Taylor＆Francis Group的交易发表。

Inhibition of cluster of differentiation 44 (CD44), a pancreatic cancer stem cell (CSC) marker, is a potential treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, we evaluated the effect of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), a gallotannin contained in various medicinal plants, on CD44 standard (CD44s) and CD44 variant 3 (CD44v3) in Mia-PaCa-2, human pancreatic cancer cells and explored the underlying mechanisms. PGG showed cytotoxic effects and inhibited the proliferation of Mia-PaCa-2 cells. It also inhibited clonogenic activity, adhesion to fibronectin, and cell migration, which are characteristics of CSCs. PGG inhibited the expression of CD44s and CD44v3 by inducing the phosphorylation of p53 and suppressing NF-κB and Foxo3. Inhibition of Foxo3 induces CD44v3 ubiquitination. Indeed, PGG increased proteasome activity and promoted CD44v3 ubiquitination. PGG downregulated the CSC regulatory factors Nanog, Oct-4, and Sox-2, which act downstream of CD44v3 signaling. These data indicate that PGG may have therapeutic effects in pancreatic cancer mediated by inhibition of CSC markers.© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.